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Structure paper

タイトル	N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2.
ジャーナル・号・ページ	Cell, Vol. 184, Issue 9, Page 2332-2347.e16, Year 2021
掲載日	2021年4月29日
著者	Matthew McCallum / Anna De Marco / Florian A Lempp / M Alejandra Tortorici / Dora Pinto / Alexandra C Walls / Martina Beltramello / Alex Chen / Zhuoming Liu / Fabrizia Zatta / Samantha Zepeda / Julia di Iulio / John E Bowen / Martin Montiel-Ruiz / Jiayi Zhou / Laura E Rosen / Siro Bianchi / Barbara Guarino / Chiara Silacci Fregni / Rana Abdelnabi / Shi-Yan Caroline Foo / Paul W Rothlauf / Louis-Marie Bloyet / Fabio Benigni / Elisabetta Cameroni / Johan Neyts / Agostino Riva / Gyorgy Snell / Amalio Telenti / Sean P J Whelan / Herbert W Virgin / Davide Corti / Matteo Samuele Pizzuto / David Veesler /
PubMed 要旨	The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about ...The SARS-CoV-2 spike (S) glycoprotein contains an immunodominant receptor-binding domain (RBD) targeted by most neutralizing antibodies (Abs) in COVID-19 patient plasma. Little is known about neutralizing Abs binding to epitopes outside the RBD and their contribution to protection. Here, we describe 41 human monoclonal Abs (mAbs) derived from memory B cells, which recognize the SARS-CoV-2 S N-terminal domain (NTD) and show that a subset of them neutralize SARS-CoV-2 ultrapotently. We define an antigenic map of the SARS-CoV-2 NTD and identify a supersite (designated site i) recognized by all known NTD-specific neutralizing mAbs. These mAbs inhibit cell-to-cell fusion, activate effector functions, and protect Syrian hamsters from SARS-CoV-2 challenge, albeit selecting escape mutants in some animals. Indeed, several SARS-CoV-2 variants, including the B.1.1.7, B.1.351, and P.1 lineages, harbor frequent mutations within the NTD supersite, suggesting ongoing selective pressure and the importance of NTD-specific neutralizing mAbs for protective immunity and vaccine design.
リンク	Cell / PubMed:33761326 / PubMed Central
手法	EM (単粒子) / X線回折
解像度	2.2 - 6.5 Å
構造データ	23577 7lxw EMDB-23577, PDB-7lxw: SARS-CoV-2 S/S2M11/S2X333 Local Refinement 手法: EM (単粒子) / 解像度: 2.8 Å 23578 7lxx EMDB-23578, PDB-7lxx: SARS-CoV-2 S/S2M11/S2L28 Local Refinement 手法: EM (単粒子) / 解像度: 3.0 Å 23579 7lxy EMDB-23579, PDB-7lxy: SARS-CoV-2 S/S2M11/S2X333 Global Refinement 手法: EM (単粒子) / 解像度: 2.2 Å 23580 7lxz EMDB-23580, PDB-7lxz: SARS-CoV-2 S/S2M11/S2L28 Global Refinement 手法: EM (単粒子) / 解像度: 2.6 Å 23581 7ly0 EMDB-23581, PDB-7ly0: SARS-CoV-2 S/S2M11/S2M28 Local Refinement 手法: EM (単粒子) / 解像度: 2.6 Å 23582 7ly2 EMDB-23582, PDB-7ly2: SARS-CoV-2 S/S2M11/S2M28 Global Refinement 手法: EM (単粒子) / 解像度: 2.5 Å EMDB-23583: SARS-CoV-2 S/S2M11/S2M24 map 手法: EM (単粒子) / 解像度: 6.5 Å EMDB-23584: SARS-CoV-2 S/S2X28 map 手法: EM (単粒子) / 解像度: 3.5 Å EMDB-23585: SARS-CoV-2 S/S2M11/S2X316 map 手法: EM (単粒子) / 解像度: 6.0 Å EMDB-23586: SARS-CoV-2 S/S2M11/S2L20 map 手法: EM (単粒子) / 解像度: 6.3 Å PDB-7ly3: Crystal structure of SARS-CoV-2 S NTD bound to S2M28 Fab 手法: X-RAY DIFFRACTION / 解像度: 3 Å
化合物	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン / N-アセチルグルコサミン ChemComp-HOH: WATER / 水 ChemComp-UNX: Unknown entry ChemComp-XYL: Xylitol / キシリト-ル / キシリトール ChemComp-SO4: SULFATE ION / 硫酸ジアニオン / 硫酸塩
由来	homo sapiens (ヒト) severe acute respiratory syndrome coronavirus 2 (SARSコロナウイルス2)
キーワード	VIRAL PROTEIN/IMMUNE SYSTEM (ウイルス性) / Antibody (抗体) / VIRAL PROTEIN (ウイルスタンパク質) / Structural Genomics (構造ゲノミクス) / Structural Genomics Consortium / SGC / Seattle Structural Genomics Center for Infectious Disease / SSGCID / VIRAL PROTEIN-IMMUNE SYSTEM complex (ウイルス性)